Intra-articular Xenotransplantation of Adipose-Derived Stromal Cells to Treat Osteoarthritis in a Goat Model

Abstract

Adipose-derived stromal cells (ASCs) have been investigated as a cell source for tissue regeneration. The purpose of this study was first to confirm if medial meniscectomy induces osteoarthritis (OA) in goats within a relative short period of time, and more importantly, to investigate if systemic treatment with immunosuppressive drugs is necessary in intra-articular ASC xenotransplantation for successful regeneration of articular cartilage and prevention of joint inflammation. Eight Korean native black goats 1-2 years of age underwent medial meniscectomy. To evaluate the gross and histological appearance of articular cartilage, knee joints were re-exposed by a medial parapatellar incision at 8 weeks. After macroscopic scoring of gross appearance, cartilage biopsy specimens 6 mm in diameter were obtained from the femoral condyle in four goats. The goats were injected with single intra-articular dose of 7910 6 human ASCs (hASCs) 7 days after the second arthrotomy. Four animals were treated with daily injections of cyclosporin A 10 mg/kg for 7 days, followed by a reduced dose of 5 mg/kg for another 7 days, while other 4 animals did not receive immunosuppressive therapy. All animals were sacrificed for analysis 8 weeks after injection of hASCs. OA was successfully induced 8 weeks after medial meniscectomy. Eight weeks after injection of hASCs, various signs of articular cartilage regeneration were observed. There were no significant macroscopic and histological differences between goats treated with cyclosporine and untreated goats. Interleukin-1ß and tumor necrosis factor-a level from synovial fluid did not differ between cyclosporinetreated and untreated goats. The results indicate that immunosuppressive therapy did not influence the result of ASC xenotransplantation to treat OA.

Adipose Stem Cells with Conditioned Media for Treatment of Acne Vulgaris Scar

“…However, cell therapy using ASCs is preferred because these cells are easy to isolate and have high relative abundance than BM-MSCs [9]. Moreover, studies suggest that transplanted ASCs accelerate wound healing by expanding the fibroblasts phenotype and increasing the supply of macrophages to the wound, enhancing granulation tissue formation [10][11][12]. Further studies showed that ASCs promote the growth of dermal fibroblasts through not only intercellular cell-to-cell contact, but also by paracrine activation of marginal cells [13][14][15][16].…”

Perspective on Intra-articular Injection Cell Therapy for Osteoarthritis Treatment

“…Human adipose stem cells (hASCs) are known to prolong the survival of ASCs and enhance anti-inflammatory effect [23]. The author has also tested if injection of hASCs in spheroid form could prolong the survival of ASCs in the joint cavity of immunosuppressed rats.…”

Multi‐Disciplinary Approaches for Cell‐Based Cartilage Regeneration

“…Nonviral, adenoviral, retroviral, and adeno‐associated virus (AAV) vectors have been used to deliver genes to AC defects using ex vivo approaches . While most studies were performed in small animals such as rats and rabbits, data from large animal (sheep or horse), which would be more predictive of human results are generally lacking …”

“…2 While most studies were performed in small animals such as rats and rabbits, data from large animal (sheep or horse), which would be more predictive of human results are generally lacking. 39 Gene Transfer of GFs for Cartilage Regeneration Gene transfer of GFs makes transduced cells secrete active peptides that can produce a more favorable environment for cartilage regeneration. Genes that would stimulate chondrogenesis or inhibit AC degeneration can be used with this type of gene therapy.…”